This application addresses broad Challenge Area (14) Stem Cells and specific Challenge Topic (14-EB- 102) Imaging Stem Cell Migration and Differentiation. The demand for advanced cell-tracking technologies is increasing in the field of stem cell therapy. Although many medical imaging modalities have been proposed to image stem cells, magnetic resonance imaging (MRI) offers a noninvasive method to visualize internal anatomical features with excellent resolution. Gadolinium-filled carbon nanocapsules, or gadonanotubes (GNTs), were discovered in our laboratories in 2005. GNTs have been shown to be superior T1-weighted MRI contrast agents, with proton relaxivities 40 times greater at 1.5 T than those of any other known Gd3+based MRI contrast agent in current clinical use. This property may allow GNTs to become the first T1-weighted MRI nanolabels for the tracking of mesenchymal stem cells (MSCs). Preliminary in vitro results show that high labeling efficiency was achieved in the absence of a transfecting agent without compromising cell viability, differentiation, and proliferation. Several studies are proposed here to optimize the labeling process, evaluate the in vivo detection of GNT-labeled MSCs, and determine how cellular internalization of GNTs may affect the behavior of MSCs. Upon successful completion of the project, it is anticipated that GNTs will be used to noninvasively label and track MSCs and other cell types in vivo via MRI with greater efficacy than other current technologies allow. PUBLIC HEALTH RELEVANCE: Stem cell-based therapies have emerged as a promising approach in regenerative medicine. The ability to track transplanted stem cells after they are injected into the body is a crucial tool because it will provide insight into the fate of the injected cells and will help investigators to determine optimal cell delivery methods and therapeutic doses. In the proposed project, we will evaluate a new approach for labeling stem cells with carbon nanotubes so they can be tracked by magnetic resonance imaging in a pig model of myocardial infarction.